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1.  Improvements to bronchoscopic brushing with a manual mapping method: A three‐year experience of 1143 cases 
Thoracic Cancer  2015;7(1):72-79.
Abstract
Background
Conventional bronchoscopy with brushing alone for diagnosing peripheral pulmonary lesions (PPLs) is of low sensitivity. A manual mapping method was introduced and evaluated in this study, which could be routinely applied with bronchoscopic brushing to improve the sensitivity for malignant PPLs.
Methods
This mapping method involves the bronchoscopist drawing the route with a series of bronchial opening sketches and marking the leading bronchus at every bifurcation point based on thin‐section computed tomography. This map is then used to guide bronchoscope insertion for brushing. A cross‐sectional study on the evaluation of this method for the diagnosis of malignant PPLs was conducted on patients from July 2010 to June 2013.
Results
The sensitivity for malignant PPLs of conventional brushing, conventional brushing with mapping on a portion of patients, and conventional brushing with mapping method increased from 17.0% to 25.8% to 31.5% (P < 0.001), respectively. For lesion sizes over 3 cm, the rate of these three groups increased from 25.1% to 38.6% to 50.9% (P < 0.001), respectively. The sensitivity of this mapping method for malignant PPLs was statistically associated with lesion size, lesion character, relationship between the lesion and the leading bronchus, linear distance between the targeted bronchus and the opening of the lobe bronchus, and accessibility (P < 0.001, P = 0.039, P < 0.001, P = 0.031, and P = 0.020, respectively).
Conclusions
The manual mapping method greatly increased the bronchoscopic brushing sensitivity for malignant PPLs compared to the conventional brushing method. During routine clinical work, it is economical and convenient for guiding bronchoscope insertion.
doi:10.1111/1759-7714.12279
PMCID: PMC4718127  PMID: 26816541
Bronchoscopic brushing; guiding bronchoscopy; lung cancer; peripheral pulmonary lesions
2.  Horizontal functional gene transfer from bacteria to fishes 
Scientific Reports  2015;5:18676.
Invertebrates can acquire functional genes via horizontal gene transfer (HGT) from bacteria but fishes are not known to do so. We provide the first reliable evidence of one HGT event from marine bacteria to fishes. The HGT appears to have occurred after emergence of the teleosts. The transferred gene is expressed and regulated developmentally. Its successful integration and expression may change the genetic and metabolic repertoire of fishes. In addition, this gene contains conserved domains and similar tertiary structures in fishes and their putative donor bacteria. Thus, it may function similarly in both groups. Evolutionary analyses indicate that it evolved under purifying selection, further indicating its conserved function. We document the first likely case of HGT of functional gene from prokaryote to fishes. This discovery certifies that HGT can influence vertebrate evolution.
doi:10.1038/srep18676
PMCID: PMC4687049  PMID: 26691285
3.  Lp-PLA2 Antagonizes Left Ventricular Healing After Myocardial Infarction by Impairing the Appearance of Reparative Macrophages 
Circulation. Heart Failure  2015;8(5):980-987.
Supplemental Digital Content is available in the text.
Background—
Healing after myocardial infarction (MI) involves the biphasic accumulation of inflammatory Ly-6Chigh and reparative Ly-6Clow monocytes/macrophages. Excessive inflammation disrupts the balance between the 2 phases, impairs infarct healing, and contributes to left ventricle remodeling and heart failure. Lipoprotein-associated phospholipase A2 (Lp-PLA2), a member of the phospholipase A2 family of enzymes, produced predominantly by leukocytes, participates in host defenses and disease. Elevated Lp-PLA2 levels associate with increased risk of cardiovascular events across diverse patient populations, but the mechanisms by which the enzyme elicits its effects remain unclear. This study tested the role of Lp-PLA2 in healing after MI.
Methods and Results—
In response to MI, Lp-PLA2 levels markedly increased in the circulation. To test the functional importance of Lp-PLA2, we generated chimeric mice whose bone marrow–derived leukocytes were Lp-PLA2–deficient (bmLp-PLA2−/−). Compared with wild-type controls, bmLp-PLA2−/− mice subjected to MI had lower serum levels of inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, and decreased number of circulating inflammatory myeloid cells. Accordingly, bmLp-PLA2−/− mice developed smaller and less inflamed infarcts with reduced numbers of infiltrating neutrophils and inflammatory Ly-6Chigh monocytes. During the later, reparative phase, infarcts of bmLp-PLA2−/− mice contained Ly-6Clow macrophages with a skewed M2-prone gene expression signature, increased collagen deposition, fewer inflammatory cells, and improved indices of angiogenesis. Consequently, the hearts of bmLp-PLA2−/− mice healed more efficiently, as determined by improved left ventricle remodeling and ejection fraction.
Conclusions—
Lp-PLA2 augments the inflammatory response after MI and antagonizes healing by disrupting the balance between inflammation and repair, providing a rationale for focused study of ventricular function and heart failure after targeting this enzyme acutely in MI.
doi:10.1161/CIRCHEARTFAILURE.115.002334
PMCID: PMC4568849  PMID: 26232205
heart failure; inflammation; macrophages; monocytes; myocardial infarction
4.  Interleukin-3 amplifies acute inflammation and is a potential therapeutic target in sepsis 
Science (New York, N.Y.)  2015;347(6227):1260-1265.
Sepsis is a frequently fatal condition characterized by an uncontrolled and harmful host reaction to microbial infection. Despite the prevalence and severity of sepsis, we lack a fundamental grasp of its pathophysiology. Here we report that the cytokine interleukin (IL)-3 potentiates inflammation in sepsis. Using a mouse model of abdominal sepsis, we show that innate response activator (IRA) B cells produce IL-3, which induces myelopoiesis of Ly-6Chigh monocytes and neutrophils, and fuels a cytokine storm. IL-3 deficiency protects mice against sepsis. In humans with sepsis, high plasma IL-3 levels associate with high mortality even after adjusting for prognostic indicators. Altogether, this study deepens our understanding of immune activation, identifies IL-3 as an orchestrator of emergency myelopoiesis, and reveals a new therapeutic target for treating sepsis.
doi:10.1126/science.aaa4268
PMCID: PMC4376966  PMID: 25766237
5.  Genetic Modification of T Cells Redirected towards CS1 Enhances Eradication of Myeloma Cells 
Purpose
Our goal is to test if CS1 could be targeted by CAR T cells to treat MM.
Experimental Design
We generated a retroviral construct of a CS1-specific CAR and engineered primary human T cells expressing the CAR. We then tested the capacity of CS1-CAR T cells to eradicate human multiple myeloma tumor cells in vitro, ex vivo and in vivo using orthotopic MM xenograft mouse models.
Results
In vitro, compared to mock-transduced T cells, upon recognizing CS1 positive MM cells, CS1-CAR-tranduced T cells secreted more IFN-γ as well as IL-2, expressed higher levels of the activation marker CD69, showed higher capacity for degranulation, and displayed enhanced cytotoxicity. Ectopically forced expression of CS1 in MM cells with low CS1 expression enhanced recognition and killing by CAR T cells. Ex vivo, CS1-CAR T cells also showed similarly enhanced activities when responding to primary MM cells. More importantly, in orthotopic MM xenograft mouse models, adoptive transfer of human primary T cells expressing CS1-CAR efficiently suppressed the growth of human MM.1S and IM9 myeloma cells and significantly prolonged mouse survival.
Conclusions
CS1 is a promising antigen that can be targeted by CAR-expressing T cells for treatment of MM.
doi:10.1158/1078-0432.CCR-13-2510
PMCID: PMC4119545  PMID: 24677374
Chimeric antigen receptor; CS1; T cells; multiple myeloma; gene therapy
6.  Bortezomib-induced unfolded protein response increases oncolytic HSV-1 replication resulting in synergistic, anti-tumor effects 
Background
Bortezomib is an FDA-approved proteasome inhibitor, and oncolytic HSV-1 (oHSV) is a promising therapeutic approach for cancer. We tested the impact of combining bortezomib with oHSV for anti-tumor efficacy.
Methods
The synergistic interaction between oHSV and bortezomib was calculated using Chou-Talalay analysis. Viral replication was evaluated using plaque assay and immune fluorescence. Western-blot assays were used to evaluate induction of ER stress and unfolded protein response (UPR). Inhibitors targeting Hsp90 were utilized to investigate the mechanism of cell killing. Anti-tumor efficacy in vivo was evaluated using subcutaneous and intracranial tumor xenografts of glioma and head and neck cancer. Survival was analyzed by Kaplan-Meier curves and two-sided log rank test.
Results
Combination treatment with bortezomib and oHSV, 34.5ENVE, displayed strong synergistic interaction in ovarian cancer, head & neck cancer, glioma, and malignant peripheral nerve sheath tumor (MPNST) cells. Bortezomib treatment induced ER stress, evident by strong induction of Grp78, CHOP, PERK and IRE1α (western blot analysis) and the UPR (induction of hsp40, 70 and 90). Bortezomib treatment of cells at both sublethal and lethal doses increased viral replication (p value <0.001), but inhibition of Hsp90 ablated this response, reducing viral replication and synergistic cell killing. The combination of bortezomib and 34.5ENVE significantly enhanced anti-tumor efficacy in multiple different tumor models in vivo.
Conclusions
The dramatic synergy of bortezomib and 34.5ENVE is mediated by bortezomib- induced UPR and warrants future clinical testing in patients.
doi:10.1158/1078-0432.CCR-14-0553
PMCID: PMC4132885  PMID: 24815720
7.  FLT3L and Plerixafor Combination Increases Hematopoietic Stem Cell Mobilization and Leads to Improved Transplantation Outcome 
Hematopoietic stem cell (HSC) transplantation has curative potential for patients with hematological malignancies. Clinically, HSCs derived from mobilized peripheral blood are used more frequently than bone marrow. However, current standard mobilizing agents yield grafts that may not contain sufficient HSCs. Here, using murine models, we discovered that FLT3L synergized with Plerixafor to mobilize phenotypically defined HSCs, and their combination (FP) was superior to G-CSF alone or in combination with Plerixafor (GP). Additionally, FP mobilized more Treg cells, NK cells, and plasmacytoid dendritic cells compared with G-CSF alone or GP. Both syngeneic and allogeneic grafts mobilized by FP led to long-term survival in transplanted mice. Collectively, FP represents a promising novel and potent mobilization regimen with potential clinical application in both the autologous and allogeneic transplantation settings.
doi:10.1016/j.bbmt.2013.11.024
PMCID: PMC3943635  PMID: 24365795
Cell mobilization; Transplantation; FLT3L; Plerixafor
8.  New insights into the fungal community from the raw genomic sequence data of fig wasp Ceratosolen solmsi 
BMC Microbiology  2015;15(1):27.
Background
To date, biologists have discovered a large amount of valuable information from assembled genomes, but the abundant microbial data that is hidden in the raw genomic sequence data of plants and animals is usually ignored. In this study, the richness and composition of fungal community were determined in the raw genomic sequence data of Ceratosolen solmsi (RGSD-CS).
Results
To avoid the interference from sequences of C. solmsi, the unmapped raw data (about 17.1%) was obtained by excluding the assembled genome of C. solmsi from RGSD-CS. Comparing two fungal reference datasets, internal transcribed spacer (ITS) and large ribosomal subunit (LSU) of rRNA, the ITS dataset discovered a more diverse fungal community and was therefore selected as the reference dataset for evaluating the fungal community based on the unmapped raw data. The threshold of 95% sequence identity revealed many more matched fungal reads and fungal richness in the unmapped raw data than those by identities above 95%. Based on the threshold of 95% sequence identity, the fungal community of RGSD-CS was primarily composed of Saccharomycetes (88.4%) and two other classes (Agaricomycetes and Sordariomycetes, 8.3% in total). Compared with the fungal community of other reported fig wasps, Agaricomycetes and Eurotiomycetes were found to be unique to C. solmsi. In addition, the ratio of total fungal reads to RGSD-CS was estimated to be at least 4.8 × 10−3, which indicated that a large amount of fungal data was contained in RGSD-CS. However, rarefaction measure indicated that a deeper sequencing coverage with RGSD-CS was required to discover the entire fungal community of C. solmsi.
Conclusion
This study investigated the richness and composition of fungal community in RGSD-CS and provided new insights into the efficient study of microbial diversity using raw genomic sequence data.
Electronic supplementary material
The online version of this article (doi:10.1186/s12866-015-0370-3) contains supplementary material, which is available to authorized users.
doi:10.1186/s12866-015-0370-3
PMCID: PMC4329198  PMID: 25885565
Fungal community; Unmapped raw data; Fig wasp; Fungal reference datasets
9.  P21-Activated Kinase 7 Mediates Cisplatin-Resistance of Esophageal Squamous Carcinoma Cells with Aurora-A Overexpression 
PLoS ONE  2014;9(12):e113989.
Aurora-A overexpression is common in various types of cancers and has been shown to be involved in tumorigenesis through different signaling pathways, yet how the deregulation affects cancer therapeutics remains elusive. Here we showed that overexpression of Aurora-A rendered esophageal cancer cells resistance to cisplatin (CDDP) by inhibiting apoptosis. By using an apoptosis array, we identified a downstream gene, p21-activated kinase 7 (PAK7). PAK7 was upregulated by Aurora-A overexpression at both mRNA and protein levels. Importantly, the expression levels of Aurora-A and PAK7 were correlated in ESCC primary samples. Chromatin immunoprecipitation (ChIP) assay revealed that binding of E2F1 to the promoter of PAK7 was significantly enhanced upon Aurora-A activation, and knockdown of transcription factor E2F1 decreased PAK7 expression, suggesting that Aurora-A regulated PAK7 through E2F1. Furthermore, we demonstrated that PAK7 knockdown led to increased apoptosis, and Aurora-A-induced resistance to CDDP was reversed by downregulation of PAK7, suggesting PAK7 was a downstream player of Aurora-A that mediated chemoresistance of ESCC cells to CDDP. Our data suggest that PAK7 may serve as an attractive candidate for therapeutics in ESCC patients with Aurora-A abnormality.
doi:10.1371/journal.pone.0113989
PMCID: PMC4250179  PMID: 25436453
10.  Diagnosis and staging of superficial esophageal precursor based on pre-endoscopic resection system comparable to endoscopic resection 
BMC Cancer  2014;14:774.
Background
Endoscopic treatments for early esophageal squamous cell carcinoma and the esophageal neoplasm are two types: endoscopic resection (ER) and ablation. Resection enables evaluation of the lesion in the ER specimens, while ablation cannot. We sought to establish a pre-ER evaluated system with a diagnostic and staging accuracy similar to ER for the development of ablation therapy.
Methods
In our study, we collected data pertaining to early esophageal cancer and esophageal neoplasm treated with ER, analyzed the pre- and post-ER data of the lesions and evaluated the diagnostic accuracy of pre-ER system compared with the gold standard.
Results
The diagnostic accuracy rate was 91% based on the pre-ER system compared with the gold standard, and 93% based on the ER diagnosis. The AUC of the pre-ER system was 0.964, while the ER examination was 0.971.
Conclusion
These results suggest that the accuracy of pre-ER system was comparable to ER. The pre-ER system enables prediction of histological diagnosis and stage of the lesions, and the choice of treatment for superficial esophageal neoplasm.
doi:10.1186/1471-2407-14-774
PMCID: PMC4213488  PMID: 25330811
Endoscopic resection (ER); Endoscopic treatment; Superficial esophageal neoplasm; Histological diagnosis
11.  CS1-Specific Chimeric Antigen Receptor (CAR)-Engineered Natural Killer Cells Enhance In Vitro and In Vivo Anti-tumor Activity Against Human Multiple Myeloma 
Leukemia  2013;28(4):917-927.
Multiple myeloma (MM) is an incurable hematological malignancy. Chimeric antigen receptor (CAR)-expressing T cells have been demonstrated successful in the clinic to treat B-lymphoid malignancies. However, the potential utility of antigen-specific CAR-engineered natural killer (NK) cells to treat MM has not been explored. In this study, we determined whether CS1, a surface protein that is highly expressed on MM cells, can be targeted by CAR NK cells to treat MM. We successfully generated a viral construct of a CS1-specific CAR and expressed it in human NK cells. In vitro, CS1-CAR NK cells displayed enhanced MM cytolysis and IFN-γ production, and showed a specific CS1-dependent recognition of MM cells. Ex vivo, CS1-CAR NK cells also showed similarly enhanced activities when responding to primary MM tumor cells. More importantly, in an aggressive orthotopic MM xenograft mouse model, adoptive transfer of NK-92 cells expressing CS1-CAR efficiently suppressed the growth of human IM9 MM cells and also significantly prolonged mouse survival. Thus, CS1 represents a viable target for CAR-expressing immune cells, and autologous or allogeneic transplantation of CS1-specific CAR NK cells may be a promising strategy to treat MM.
doi:10.1038/leu.2013.279
PMCID: PMC3967004  PMID: 24067492
CS1; Chimeric Antigen Receptor; NK Cells; Multiple Myeloma
12.  Macrophage inhibitory factor 1 acts as a potential biomarker in patients with esophageal squamous cell carcinoma and is a target for antibody-based therapy 
Cancer Science  2014;105(2):176-185.
Macrophage inhibitory factor 1 (MIC1) is frequently altered in various cancers. The aim of this study was to investigate the clinical significance of MIC1 for esophageal squamous cell carcinoma (ESCC). Serum MIC1 of 286 ESCC and 250 healthy subjects was detected, the diagnostic performance was assessed and compared with SCC, CEA, CA199 and CA724, and the value as a prognostic indicator was also evaluated. The expression of MIC1 in ESCC cell lines, tissues were detected, and the inhibition of MIC1 antibody on ESCC was carried out in vitro and in vivo. The results showed that the serum MIC1 of ESCC was significantly higher than normal groups (P < 0.001), and was positively associated with tumor invasion (P = 0.030) as well as lymph node metastasis (P = 0.007). The sensitivity of MIC1 was significantly better than SCC, CEA, CA199 and CA724, especially for stage I ESCC. Patients with higher serum MIC1 also had a poorer prognosis in relapse-free (P = 0.050) and tumor-specific survival (P = 0.005). In vitro studies showed that the expression of MIC1 was upregulated in 37.5% (3/8) ESCC cell lines and 45% (18/40) tissues, and the transcription of MIC1 in tumor tissues was significantly higher than paired adjacent normal tissues (P = 0.001). The antibody of MIC1 inhibited the tumor growth (P < 0.001), and showing preference for tumor tissues in xenograft model. The decreased formation of neovascularization lumen may be involved in the mechanism. We conclude that MIC1 plays an important role in the progression of ESCC and can serve as a potential biomarker and therapeutic target for ESCC.
doi:10.1111/cas.12331
PMCID: PMC4317821  PMID: 24383865
Diagnosis; esophageal squamous cell carcinoma; macrophage inhibitory factor 1; prognosis; target
13.  Obligate mutualism within a host drives the extreme specialization of a fig wasp genome 
Genome Biology  2013;14(12):R141.
Background
Fig pollinating wasps form obligate symbioses with their fig hosts. This mutualism arose approximately 75 million years ago. Unlike many other intimate symbioses, which involve vertical transmission of symbionts to host offspring, female fig wasps fly great distances to transfer horizontally between hosts. In contrast, male wasps are wingless and cannot disperse. Symbionts that keep intimate contact with their hosts often show genome reduction, but it is not clear if the wide dispersal of female fig wasps will counteract this general tendency. We sequenced the genome of the fig wasp Ceratosolen solmsi to address this question.
Results
The genome size of the fig wasp C. solmsi is typical of insects, but has undergone dramatic reductions of gene families involved in environmental sensing and detoxification. The streamlined chemosensory ability reflects the overwhelming importance of females finding trees of their only host species, Ficus hispida, during their fleeting adult lives. Despite long-distance dispersal, little need exists for detoxification or environmental protection because fig wasps spend nearly all of their lives inside a largely benign host. Analyses of transcriptomes in females and males at four key life stages reveal that the extreme anatomical sexual dimorphism of fig wasps may result from a strong bias in sex-differential gene expression.
Conclusions
Our comparison of the C. solmsi genome with other insects provides new insights into the evolution of obligate mutualism. The draft genome of the fig wasp, and transcriptomic comparisons between both sexes at four different life stages, provide insights into the molecular basis for the extreme anatomical sexual dimorphism of this species.
doi:10.1186/gb-2013-14-12-r141
PMCID: PMC4053974  PMID: 24359812
14.  NK cells impede glioblastoma virotherapy via NKp30 and NKp46 natural cytotoxicity receptors 
Nature medicine  2012;18(12):1827-1834.
The role of the immune response to oncolytic Herpes Simplex viral (oHSV) therapy for glioblastoma is controversial. Within hours of oHSV infection of human or syngeneic glioblastoma in mice, activated natural killer (NK) cells are recruited to the site of infection. This response significantly diminished the efficacy of glioblastoma virotherapy. oHSV-activated NK cells coordinated macrophage and microglia activation within tumors. In vitro, human NK cells preferentially lysed oHSV-infected human glioblastoma cell lines. This enhanced killing depended on NK cell natural cytotoxicity receptors (NCR) NKp30 and NKp46, whose ligands were up-regulated in oHSV-infected glioblastoma cells. HSV titers and oHSV efficacy were increased in Ncr1−/− mice and in a Ncr1−/− NK cell adoptive transfer model of glioma, respectively. These in vitro and in vivo (mouse) results demonstrate that glioblastoma virotherapy is partly limited by an antiviral NK cell response involving specific NCRs, uncovering novel potential targets to enhance cancer virotherapy.
doi:10.1038/nm.3013
PMCID: PMC3668784  PMID: 23178246
Herpes simplex virus; gene therapy; oncolytic virus; brain tumor; microglia; macrophages
15.  Curcumin Down-Regulates DNA Methyltransferase 1 and Plays an Anti-Leukemic Role in Acute Myeloid Leukemia 
PLoS ONE  2013;8(2):e55934.
Bioactive components from dietary supplements such as curcumin may represent attractive agents for cancer prevention or treatment. DNA methylation plays a critical role in acute myeloid leukemia (AML) development, and presents an excellent target for treatment of this disease. However, it remains largely unknown how curcumin, a component of the popular Indian spice turmeric, plays a role in DNA hypomethylation to reactivate silenced tumor suppressor genes and to present a potential treatment option for AML. Here we show that curcumin down-regulates DNMT1 expression in AML cell lines, both in vitro and in vivo, and in primary AML cells ex vivo. Mechanistically, curcumin reduced the expression of positive regulators of DNMT1, p65 and Sp1, which correlated with a reduction in binding of these transcription factors to the DNMT1 promoter in AML cell lines. This curcumin-mediated down-regulation of DNMT1 expression was concomitant with p15INK4B tumor suppressor gene reactivation, hypomethylation of the p15INK4B promoter, G1 cell cycle arrest, and induction of tumor cell apoptosis in vitro. In mice implanted with the human AML MV4–11 cell line, administration of curcumin resulted in remarkable suppression of AML tumor growth. Collectively, our data indicate that curcumin shows promise as a potential treatment for AML, and our findings provide a basis for future studies to test the clinical efficacy of curcumin – whether used as a single agent or as an adjuvant – for AML treatment.
doi:10.1371/journal.pone.0055934
PMCID: PMC3572185  PMID: 23457487
16.  Outcomes from a prospective trial of endoscopic radiofrequency ablation of early squamous cell neoplasia of the esophagus 
Gastrointestinal endoscopy  2011;74(6):1181-1190.
Background
Radiofrequency ablation (RFA) is safe and effective for eradicating neoplasia in Barrett’s esophagus.
Objective
Evaluate RFA for eradicating early esophageal squamous cell neoplasia (ESCN) defined as moderate- and high-grade squamous intraepithelial neoplasia (MGIN, HGIN) and early flat-type esophageal squamous cell carcinoma (ESCC).
Design
Prospective cohort study.
Setting
Tertiary referral center.
Patients
Esophageal unstained lesions (USLs) were identified using Lugol’s chromoendoscopy. Inclusion: at least 1 flat (type 0-IIb) USL ≥3cm, USL-bearing esophagus ≤12 cm, and a consensus diagnosis of MGIN, HGIN, or ESCC by two expert GI pathologists. Exclusion: prior endoscopic resection or ablation, stricture, or any non-flat mucosa.
Interventions
Circumferential RFA creating a continuous treatment area (TA) including all USLs. At 3-month intervals thereafter, chromoendoscopy with biopsies, followed by focal RFA of USLs, if present.
Main outcome measures
Complete response (CR) at 12 months, defined as absence of MGIN, HGIN or ESCC in TA; CR after one RFA session; neoplastic progression from baseline; and adverse events.
Results
29 patients (14 male, mean age 60.3 years) with MGIN (18), HGIN (10), or ESCC (1) participated. Mean USL length was 6.2 cm (TA 8.2 cm). At 3-months, after one RFA session, 86% of patients (25/29) were CR. At 12-months, 97% (28/29) of patients were CR. There was no neoplastic progression. There were 4 strictures, all dilated to resolution.
Limitations
Single center study with limited number of patients.
Conclusions
In patients with early ESCN (MGIN, HGIN, flat-type ESCC), RFA was associated with a high rate of histological complete response (97% of patients), no neoplastic progression, and an acceptable adverse event profile.
doi:10.1016/j.gie.2011.05.024
PMCID: PMC3505032  PMID: 21839994
17.  Suppression of Aurora-A oncogenic potential by c-Myc downregulation 
Experimental & Molecular Medicine  2010;42(11):759-767.
The abnormality of serine/threonine kinase Aurora-A is seen in many types of cancers. Although in physiological context it has been shown to play a vital role in cellular mitosis, how this oncogene contributes to tumorigenesis remains unclear. Here we demonstrate that Aurora-A overexpression enhances both the expression level and transcriptional activity of c-Myc. The inhibition of c-Myc expression by RNA interference significantly impaired the oncogenic potential of Aurora-A, resulting in attenuated cellular proliferation and transformation rates as well as fewer centrosomal aberrations. Furthermore, downregulation of c-Myc effectively overcame Aurora-A-induced resistance to cisplatin in esophageal cancer cells. Taken together, our results suggest an important role for c-Myc in mediating the oncogenic activity of Aurora-A, which may in turn allow for future targeting of c-Myc as a potential therapeutic strategy for tumors with Aurora-A overexpression.
doi:10.3858/emm.2010.42.11.077
PMCID: PMC2992855  PMID: 20890087
aurora kinase; neoplasms; proto-oncogene proteins c-myc; RNA interference
19.  Evidence of human papilloma virus infection and its epidemiology in esophageal squamous cell carcinoma 
AIM: To look for the evidence of human papilloma virus (HPV) infection in esophageal squamous cell carcinomas (ESCC) and to investigate the potential role and epidemiology of HPV infection in the pathogenesis of esophageal carcinomas in Henan emigrants.
METHODS: Papilloma virus(PV)and HPV were determined by UltrasensiveTM S-P immunohistochemistry (IHC) and in situ hybridization (ISH) in esophageal carcinoma tissues (82 cases) and the normal mucosa (40 cases).
RESULTS: IHC revealed that the positive rate of PV was 75.0%, 68.18% and 72.5% respectively while the HPV (16/18-E6) positive rate was 45.0%, 36.36%, 37.5%, respectively in esophageal carcinoma tissue specimens from Henan emigrants,the local citizens and patients in Hubei Cancer Hospital. The PV and HPV (16/18-E6) were negative in all normal esophageal mucosa specimens. No correlation was found between HPV in esophageal squamous cell carcinoma tissues and in grade 1-3 esophageal squamous cell carcinoma cells. In situ hybridization showed that the HPV (16/18) DNA positive rate was 30.0%, 31.8%, 25.0%, respectively in the 3 groups of samples. No positive hybridization signal was found in 40 normal esophageal mucosa specimens. The positive rate of HPV (16/18) DNA in the esophageal carcinoma specimens was significantly higher than that in normal mucosa specimens (P < 0.05). The positive rate was not different among the 3 groups of esophageal carcinoma tissue specimens (P >0.05).
CONCLUSION: HPV infection is high in esophageal carcinoma of Henan emigrants, local residents and patients in Hubei Cancer Hospital. HPV is closely related with esophageal squamous cell carcinoma. HPV infection may play an important role in esophageal squamous cell carcinoma.
doi:10.3748/wjg.v12.i9.1352
PMCID: PMC4124309  PMID: 16552800
Human papillomavirus; Esophageal squamous cell carcinoma; Immunohistochemistry; in situ hybridization

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